omega-(n-methyl-2, 6-dialkylanilino) alkyl halides



United States PatentO 2,921,094 o:-(N-METHYL-Z,6-DIALKYLANILINO)ALKYL HALIDES Seymour L. Shapiro, Hastings on Hudson, and Louis Freedman, Bronxville, N.Y., assignors to US. Vitamin & Pharmaceutical Corporation, a corporation of Dela- Ware No Drawing. Application January 17, 1958 Serial No. 709,446 I 6 Claims. (Cl. 260-577) This invention is concerned with w-(N-methyl'-2,6-di- I alkylanilino)alkyl halides having the following formula:

wherein R is methyl or a straight chain lower alkyl group and Y is a bivalent straight chain hydrocarbon linking element which may be saturated or unsaturated and which contains at least three carbon atoms and not more than twelve carbon atoms and especially three to six carbon atoms, and X is halogen.

The compounds of this invention are of utility per se i in view of their pharmacological properties, particularly as ganglionic blocking agents, hypotensiv'e agents, and central nervous system depressants.

The compounds of this invention also have distinct chemical properties in thatin view of steric factors as- These quaternized derivatives of the w-(N-methyl-2,6- dialkylanilino)alkyl halides with tertiary amines are also to be considered within the purview of this invention.

The quaternization is desirably carried out in an inert organic solvent such as acetonitrile, nitromethanol, iso- Patented Jan. 12, 1960 2 propyl alcohol and the like, and at reaction temperatures ranging from 20 C to C.

Ihe anilinoalkyl halide compounds of this invention are prepared" by reaction of'the N methyl 2,6-dialkylaniline with an excess of a dihalide of the type XY-X, wherein Y and X have the samesignificance as described above. Desirably, potassium; iodide is added to expedite the reaction.

As more specifically illustrative of the preparation of the compounds contemplated by this invention, the following specific examples of the preparation of specific compounds contemplated by this invention will serve to exemplify the preparation of all the several compounds, since all of the several compounds contemplated will be prepared in the same manner with the selection of starting materials required for the production of any particular desired specific compound.

EXAMPLE I N-methyl-2,6-dimethylaniline EXAMPLE II N-niethyl-Zd-diethyldniling In a manner similar to that described above using 2,6- diethylaniline, the product was obtained in 81% yield, boiling at 229-231 C.

Analysis-Calcd. for C H N: C, 80.9; H, 10.5; N, 8.6. Found: C, 80.8; H, 10.7; N, 8.6.

EXAMPLE III- N 6-br0mohexyl -N -methyl-2,6-dimethylaniline A mixture of 9.25 g. (0.0685 mole) of N-methyl-2,6- dimethylaniline, 33.4 g. (0.137 mole) of 1,6-dibromohexane and 50 mg. of potassium iodide was heated in an oil bath at Cpf or 25 minutes. After addition of 100 m1. of water, the cooled mixture was made alkaline with 6 N sodium hydroxide and promptly extracted with three 100 ml. portions of ether. The combined ether extracts were dried (magnesium sulfate), filtered, the ether removed and the residue distilled. The product, 7.1 g. (35% was Obtained, boiling at 146.15 4 C./0.5,mm.

AnalysisCalcd. for C H BrN: N,4.7. Found: N, 4.6.

EXAMPLE IV A mixture of 1.79 g. (0.007 mole) of N-(S-bromo- 'propyl)-N-methyl-2,6-dimethylaniline and 0.73 g. (0.0074

mole) of N-methylpiperidine in ml. of acetonitrile was heated under reflux for one hour. On cooling, 0.95 g. (38%) of colorless crystals were filtered oif, washed with ethylacetate and dried in vacuo, M.P. 185187.5 C.

. "4' 1' Having described our invention, what we claim as new and desire to secure by Letters Patent is: 1. The compound having the formula Analysis-Calcd. for C H BrN c, 60.8; H, 8.7; 5 N, 7.9; Br, 22.5. Found: C, 60.9; H, 8.8; N, 7.9; Br, 22.6.

Typifying, but not limiting the products herein, there is. reported in Table I, a series of compounds with their R physical properties, which have been prepared following the procedure described in Example III. wherein R is selected from the group consisting of methyl I Turn I w-(N-methy1-2,6-d1a1ky1ani1ino)alkyl halides r R Y X B.P., 0 mm. Formula 7 Press.

on} (CH )3 Br 90-04 0.2 CmHmBrN 0113- (CH2) 4- Cl 94-98 0. 07 CISHZUCIN C a- -(CH2)4 Br 98-102 0.18 CisHzuBrN OH1- CH2) 5- Bl 124-128 0. 4 C HHQZBI'N OHa- (CH2)5 Br 146-154 O. 5 CH24BrN CHs- CHnCH=CHCHz Cl 92-96 0.08 CraHtsClN CQH5 )3 B1 108-112 0.1 CuHzzBIN CzH -o1120H=oH oH, 01 104-106 0.26 CraHzzClN The compounds of the type shown turn be reacted with lower alkyl tertiary amines which may be exemplified .by tri-methylamine, t'ri ethylamine', N- methylpiperidine, N-methylpyrrolidine, N-methylmorpholine and the like as has been shown in the foregoing equation.

Examples of such preparations are typified by compounds prepared and described in Table II following the procedure of Example 'IV. The group N Am represents the lower alkyl tertiary amine used to form the quaternary salt;

Examples of such preparations are typified by compounds prepared and described in Table 11 following the procedure of Example IV. The group N Am represents the lower alkyl tertiary amine used to form the in Table I can in 30 and ethyl, Y is a member of the group consisting of a straight chain bivalent saturated hydrocarbon linking element containing from three to six carbon atoms and CH -CH=CH-CH and X is a member of the group consisting of chlorine and bromine.

2. The compound 3. The compound quaternary salt.

, CH: TABLE II 4. The compound Ci u R CH3 i711,

1 NCHi-CH CH CHr-Cl R Y N Am X M.P 0 Formula QH;- (CH2)atriethylamine Br 142-144 cmHsa r s CH (CH;)3 N-methylpiperidine Br 185-187 GuaHn r a CH3 (CH2)4- triethylamine Br -152 CraHssBlNZ CHa (CHz)5 N-methy1piperidine. Br 133-134 C21 a1 I t from the spirit and, scope thereof, and it is to be understood that we limit ourselves only as defined in the appended claims.

5. The compound CH3 6. The compound CH3 (EH3 -N-(CHz) 5Br (References on following page) References Cited in the file of this patent UNITED STATES PATENTS Hartmann Oct. 7, 1930 Nusslein et a1 Mar. 11, 1941 5 Stayner Nov. 16, 1954 Bruson Jan. 18, 1955 FOREIGN PATENTS Switzerland Jan. 16, 1939 Great Britain July s, 1948 10 6 OTHER REFERENCES Braun et al.: Deut. Chem. Gesell. (Berichte), v01.

70-B, page 985 (1937).

Munch et a1.: I. of the Am. Chem. Soc., vol. 68, 1297-8 (1946).

Boon: Chem. Absts., vol. 41, 5447g (1947).

Everett et al.: J. of the Chem. Soc. (1949), page 1977.

Babayan et al.: Chem. Absts., v01. 49, page 11,5760 (1955). 

1. THE COMPOUND HAVING THE FOMULA 